Complement-mediated regulation of tissue factor activity in endothelium.

Abstract

SummaryInflammation and immunity may be associated with endothelial cell (EC) injury and thrombus formation . We explored the mechanisms through which a humoral immune response directed against the endothelium might promote coagulation . Using the interaction ofanti-EC antibodies and complement (C) with cultured EC as a model, we studied the expression and function of tissue factor, a cofactor for factor VIIa-mediated conversion offactor X to Xa. Exposure of EC to anti-EC antibodies and C in sublytic amounts stimulated the synthesis of tissue factor over a period of 16-42 h. Cell surface expression of tissue factor activity required activation of C and assembly of the membrane attack complex, because expression was inhibited by soluble CR1 and was not detected in the absence of C8. Elaboration of tissue factor messenger RNA was observed over a period of 8-30 h and required protein synthesis . Expression of tissue factor was not a direct consequence of the action of C on the EC but was a secondary response that required as an intermediate step the release of interleukin 1o, an early product of the EC response to C activation. These findings suggest that, after the assembly ofmembrane attack complex on EC, the production of tissue factor and initiation of coagulation in a blood vessel depend on the production ofinterleukin la and on its availability to stimulate affected EC.

Induction of interleukin‐1 and subsequent tissue factor expression by anti‐proteinase 3 antibodies in human umbilical vein endothelial cells

“…Del Papa et a1 showed that AECA induced endothelial synthesis of IL-lp, leading to ELAM-1 expression (38). Saadi et a1 showed that complement-induced TF production by endothelial cells was mediated by IL-la (36). This role of IL-la is also supported by data from Carlsen et a1 (40), who showed that recombinant IL-la induced a concentrationdependent increase in endothelial cell TF activity, an effect that was stronger at 6 hours than at 16 hours.…”

“…This potentially indicated that the effect observed with anti-PR3-stimulated HUVEC involved intracellular pathways that require protein synthesis (Figures 2 and 3). To identify this intracellular pathway, we investigated whether IL-1 a mediated the response (36)(37)(38). We therefore looked for IL-la synthesis by measuring IL-la mRNA by RT-PCR in anti-PR3-stimulated HUVEC.…”

Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59

“…Such events may create medullary vascular congestion and accumulation of intravascular leukocytes. Additionally, activation and injury of endothelial cells may induce a procoagulant response (34), leading to the formation of thrombus in the microvasculature. This congestion and thrombosis may in turn impair oxygen delivery to the outer medulla, resulting in an "extension phase" of ischemia which compounds the initial IR assault (17).…”

Acute Humoral Xenograft Rejection: Destruction of the Microvascular Capillary Endothelium in Pig-to-Nonhuman Primate Renal Grafts

“…Laboratory Investigation • June 2000 • Volume 80 • Number 6 develop in discordant porcine xenografts as a consequence of complement activation, inflammation, and the secondary development of a procoagulant state Ierino et al, 1998;Lawson and Platt, 1996;Robson et al, 1996;Saadi et al, 1995). Alternatively, vascular thrombosis may be promoted by cross-species molecular incompatibilities between activated primate coagulant factors and donor anticoagulant proteins expressed on the graft vasculature .…”